System and method for non-invasive monitoring of cerebral tissue hemodynamics

ABSTRACT

A method and system are provided which are useful for the non-invasive determination and monitoring of cerebral blood oxygenation in a patient. The system comprises a first module for optically generating at least first and second internal jugular venous output signals against time at at least first and second wavelengths of light; and a second module for generating first and second cardiac arterial output signals at the first and second wavelengths of light, respectively. The system may additionally include a third module for optically generating at least first and second external jugular venous output signals against time at at least first and second wavelengths of light, and one or more cerebral modules for optically generating at least first and second local cerebral output signals against time at at least first and second wavelengths of light. The system includes a signal processing means adapted to calculate average cerebral, arterial, venous scalp and local cerebral blood oxygenation values based on the output from each of the modules.

This application is a continuation-in-part application of U.S. Ser. No.12/713,368 filed Feb. 26, 2010 which claims the benefit of U.S.Provisional Application No. 61/202,441, filed Feb. 27, 2009, andincorporates such provisional application in its entirety by reference.

FIELD OF THE INVENTION

The present invention is related to techniques for monitoring vitalfunctions of the human body, including cerebral tissue hemodynamics. Itrelates, in particular, to an optical method and system for thenon-invasive and continuous monitoring of cerebral parameters such ascerebral tissue oxygenation.

BACKGROUND OF THE INVENTION

Monitoring cerebral tissue oxygenation or oxygen consumption is criticalfor the management of patients with traumatic brain injury and patientsundergoing cardiac by-pass surgeries. Insufficient cerebral tissueoxygen consumption over a few minutes can lead to irreversible, severe,neurological damage. Cerebral oxygen consumption can be estimatedthrough the differences between arterial and cerebral venous bloodoxygen saturation. Pulse Oximetry (such as Masimo Radical-7™) is theclinical standard for non-invasive monitoring of arterial blood oxygensaturation at the finger tip. However, the determination of cerebralvenous blood saturation is conducted using highly invasive venouscatheters such as the jugular vein bulb catheter. Non-invasive methodssuch as pulse oximtery cannot be used to obtain cerebral venous bloodoxygenation because, unlike arterial vessels, venous blood vessels arepassive and without pulsation.

Cerebral tissue oximetry has also been developed based on near infraredspectroscopy to non-invasively measure tissue oxygenation at varioussites on the head (such as INVOS Cerebral Oximeter of Somanetics Inc.).However, it is difficult for light to penetrate through the skull andreach cerebral tissues. As a result, the device is limited to measuringonly a small spot on the surface of the cortical tissue which does notnecessarily represent the overall cerebral tissue oxygenation, e.g.especially tissues deep inside brain.

Accordingly, there is a need to develop a means to accurately andnon-invasively determine cerebral tissue dynamics.

SUMMARY OF THE INVENTION

The present invention provides a novel method of determining cerebraltissue oxygenation, as well as a system useful for such a determination.The method includes optically obtaining an output signal of internaljugular venous blood at at least two different wavelengths, separatingfrom these output signals the cardiac arterial pulse portion of thesignal to provide an output signal of cerebral venous blood at theselected wavelengths, and determining the cerebral tissue oxygenationbased on the cerebral venous output signals.

Thus, in one aspect of the invention, a method for determining cerebraltissue oxygenation in a patient is provided comprising the steps of:

1) generating at least first and second jugular venous output signalsagainst time based on the reflection of first and second wavelengths oflight, respectively, from an external tissue site on the patient in theproximity of the internal jugular vein;

2) obtaining corresponding first and second cardiac arterial outputsignals using a pulse oximeter for the first and second wavelengths oflight, respectively, from the patient, and

3) determining average cerebral tissue oxygenation based on the firstand second cerebral venous output signals, and arterial tissueoxygenation based on the first and second cardiac arterial outputsignals with a processor.

In another aspect of the invention, a method is provided comprising thesteps of:

1) determining scalp venous blood oxygenation by generating at leastfirst and second output signals of change in blood volume as current orvoltage over time using at least one photodetector based on thereflection or transmission of at least first and second wavelengths oflight from at least one light source, wherein the light is applied tothe neck of the patient in the proximity of the external jugular vein;

2) determining the average cerebral venous oxygenation by generating atleast first and second output signals of change in blood volume ascurrent or voltage over time using at least one photodetector based onthe reflection or transmission of at least first and second wavelengthsof light from at least one light source, wherein the light is applied tothe neck of the patient in the proximity of the internal jugular vein;

3) determining local cerebral blood oxygenation at one or more cerebralsites by generating at least first and second output signals of changein blood volume as current or voltage over time using at least onephotodetector based on the reflection or transmission of at least firstand second wavelengths of light from at least one light source, whereinthe light is applied to the head of the patient in the proximity of theone or more cerebral sites;

4) determining cerebral arterial blood oxygenation by generating atleast first and second cardiac arterial output signals over time using apulse oximeter for the first and second wavelengths of light; and

5) comparing the local cerebral blood oxygenation to the averagecerebral blood oxygenation, scalp venous blood oxygenation and scalparterial oxygenation using a processor to identify changes in one ormore of these and thereby detect cerebral ischemia.

In another aspect, a system useful to determine and monitor cerebraltissue oxygenation in a patient is provided comprising:

1) a first module for optically generating first and second jugularvenous output signals against time at first and second wavelengths oflight, respectively, from the patient;

2) a second module for generating first and second cardiac arterialoutput signals at the first and second wavelengths of light,respectively, from the patient; and

3) a signal processing means adapted to calculate average cerebraltissue oxygenation based on the first and second cerebral venous outputsignals, and arterial tissue oxygenation based on the first and secondcardiac arterial output signals.

These and other aspects of the present invention will become apparent byreference to the detailed description that follows, and the drawings inwhich:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a top view of an embodiment of a device useful toobtain a jugular venous output signal;

FIG. 2 is a top view of another embodiment of the device of FIG. 1;

FIG. 3 is a top view of further embodiments of the device of FIG. 1;

FIG. 4 is a block diagram illustrating a system according to an aspectof the invention;

FIG. 5 is a block diagram also illustrating a system according to theinvention;

FIG. 6 illustrates the use of the system;

FIG. 7 illustrates waveforms obtainable from the system;

FIG. 8 visually illustrates results obtained using the present systemand method; and

FIG. 9 illustrates an embodiment according to an aspect of theinvention.

DETAILED DESCRIPTION OF THE INVENTION

An optical method for determining cerebral tissue oxygenation in apatient is provided. The method includes optically generating at leastfirst and second jugular venous output signals against time based on thereflection of at least first and second wavelengths of light from anexternal tissue site on the patient in the proximity of the internaljugular vein. Cardiac arterial output signals at the first and secondwavelengths are also obtained from the patient and subtracted from thefirst and second jugular venous output signals to generate first andsecond cerebral venous output signals from which cerebral tissueoxygenation is calculated.

The invention utilizes the fact that the internal jugular vein containscerebral venous blood returning to the right atrium of the heart. Aninternal jugular venous output signal can be determined within theinternal jugular vein by measuring light reflected from an externaltissue site on a patient in the proximity of the internal jugular vein.However, the signal obtained from the jugular vein will also incorporatea cardiac arterial output signal, e.g. from the carotid artery (due tothe close proximity of the internal jugular vein and carotid artery).Accordingly, the portion of the signal due to carotid artery pulsationis determined and subtracted from the jugular vein signal to obtain acerebral venous output signal from which cerebral tissue oxygenation maybe calculated using, for example, modified Beer Lambert's law, as willbe described.

The term “output signal” as it is used herein with respect to jugularvenous output signals, cardiac arterial output signals and cerebralvenous output signals, refers to a current/voltage signal whichcorresponds to the optical signal obtained as a result of the pulse ineach of the internal jugular vein, the carotid artery and the cerebralveins (determined by removing the cardiac arterial optical signal fromthe jugular venous optical signal), respectively.

In a first step of the method, jugular venous output signals againsttime are optically obtained by directing light of at least two differentwavelengths, e.g. a first wavelength and a second wavelength, each inthe range of 400 nm to 1000 nm, to an external tissue site on a patientthat is in the proximity of the internal jugular vein, detecting lightreflected from the tissue site in each case, e.g. from the first andsecond wavelengths, including light transmitted through the tissue site,and translating the detected light into a first and second jugular veinoutput signals against time. For the determination of cerebral tissueoxygenation, for example, first and second wavelengths of light areselected between 400 and 1000 nm. In one embodiment, the selectedwavelengths of light may be 690 nm, for deoxygenated haemoglobincontent, and 830 nm, for oxygenated haemoglobin content. As one of skillin the art will appreciate, more than two wavelengths of light may beutilized in this method. The use of more than two wavelengths mayprovide a more accurate result, e.g. reduce error. An example of adevice useful to obtain such first and second jugular vein outputsignals will be described.

In a second step of the method, in order to exclude extraneous cardiacarterial output, e.g. such as from the carotid artery, from the jugularvein output signals obtained, the cardiac arterial output signal of thepatient is determined at each wavelength and translated into an arterialoutput signal against time. Cardiac arterial output in a patient may bedetermined using well-established techniques, including for example,pulse oximetry in which arterial pulse is optically determined in apatient and translated into a cardiac arterial output signal.

Once a cardiac arterial output signal is obtained at each of theselected wavelengths, e.g. first and second wavelengths, it is separatedor removed from each of the first and second jugular venous outputsignals, respectively, to generate first and second cerebral venousoutput signals. This separation of the cardiac arterial output signalfrom the first and second jugular venous output signals is generallyeffected digitally, using a digital signal processor, as will bedescribed, incorporating an appropriate algorithm for this purpose.

Cerebral tissue oxygenation may then be calculated based on the firstand second cerebral venous output signals using modified Beer Lambert'slaw as follows:

Modified Beer Lambert's Law

The first cerebral venous pulse signal (e.g. current) may be expressedas:

$\begin{matrix}{I_{\lambda_{1}} = {I_{0,\lambda_{1}}e^{{{- {B{\lbrack{{ɛ_{{Hb},\lambda_{1}} \cdot {({C_{Hb} + {\Delta\; C_{Hb}}})}} + {ɛ_{{HbO},\lambda_{1}} \cdot {({C_{HbO} + {\Delta\; C_{HbO}}})}}}\rbrack}}}L} + A}}} & (1)\end{matrix}$where:I_(λ) ¹ is the output signal obtained at a first wavelength of light λ₁,I_(0×λ) ₁ is the signal from the light source at the first wavelengthλ₁,C_(Hb),C_(HbO) are the concentrations of deoxygenated and oxygenatedhaemoglobin, respectively, of steady tissue medium blood;ΔC_(Hb)ΔC_(HbO) are the changes in the concentrations of deoxygenatedand oxygenated haemoglobin, respectively, derived from measured valuesas shown in equations 2-4 which follow;ε_(Hb,λ) ₁ ,ε_(HbO,λ) ₁ are the absorption properties of deoxygenatedand oxygenated haemoglobin, respectively, at the first wavelength λ₁ forthe purposes of calculating blood oxygen saturation. Blood saturation ofother chromophores can also be calculated by substituting into theequation the appropriate extinction coefficients (ε) for the selectedchromophore including, for example, water, cytochromes such ascytochrome oxides, and cholesterol; andA. B are constants determined by boundary conditions.

The relative change in signal from the signal emitted by a light sourceto the detected signal is represented for a first wavelength by:

$\begin{matrix}{{{\Delta\; I_{\lambda_{1}}} = e^{{- {B{\lbrack{{ɛ_{{Hb},\lambda_{1}} \cdot {({\Delta\; C_{Hb}})}} + {ɛ_{{HbO},\lambda_{1}} \cdot {({\Delta\; C_{HbO}})}}}\rbrack}}}L}};} & (2)\end{matrix}$or asOD _(λ) ₁ =ln(ΔI _(λ) ₁ )=−B(εHb,λ ₁ ·ΔC _(Hb)+ε_(HbO,λ) ₁ ·ΔC_(HbO))  (3).

Similarly, the change in signal between emitted and detected signal fora second light wavelength is represented by:OD _(λ) ₂ =ln(ΔI _(λ) ₂ )=−B(ε_(Hb,λ) ₂ ·ΔC _(Hb) +εHbO,λ ₂ ·ΔC_(HbO))  (4)

Cerebral blood oxygenation derived from the cerebral venous outputsignal is then determined using the following equation:

$\begin{matrix}\begin{matrix}{{S_{jv}O_{2}} = \frac{\Delta\; C_{HbO}}{{\Delta\; C_{Hb}} + {\Delta\; C_{HbO}}}} \\{= {\frac{{ɛ_{{Hb},\lambda_{1}} \cdot {OD}_{\lambda_{2}}} - {ɛ_{{Hb},\lambda_{2}} \cdot {OD}_{\lambda_{1}}}}{{\left( {ɛ_{{Hb},\lambda_{1}} - ɛ_{{HbO},\lambda_{1}}} \right) \cdot {OD}_{\lambda_{2}}} - {\left( {ɛ_{{Hb},\lambda_{2}} - ɛ_{{HbO},\lambda_{2}}} \right) \cdot {OD}_{\lambda_{1}}}}.}}\end{matrix} & (5)\end{matrix}$

Alternatively, cerebral oxygenation based on internal jugular venousoutput and cardiac arterial oxygenation based on cardiac arterial outputare each determined and cerebral oxygenation consumption is estimated bythe difference of cardiac arterial oxygenation and internal jugularvenous oxygenation.

A device 100 useful to obtain the first and second output signals of theinternal jugular vein is shown in FIG. 1, and as described in WO2008/098353 A1. The device comprises at least two light-emittingcomponents 120, each emitting light of a different wavelength within therange of 400 nm to 1000 nm. The device also comprises a light-receivingcomponent 130 for each light-emitting component 120 adapted to receivethe emitted or reflected light at a given wavelength.

The light emitting component (e.g. light source 120 or transmittingoptical fibres 124) and light receiving component (e.g. photodetector130 or receiving optical fibres 126) are set in a patch probe 128, andmay be arranged as shown in FIG. 1; however, as one of skill in the artwill appreciate, alternative arrangements of the light-emittingcomponents and light-receiving components exist which will not affectthe function of the device 100. For example, the device 100 may comprisemultiple patch probes 128, each of which includes a light-emittingcomponent and a light-receiving component. Alternatively, the device 100may comprise a single patch 128 including multiple light-emittingcomponents and light-receiving components. In another alternative, thedevice 100 may comprise a first patch 128 with one or morelight-emitting components and light-receiving components, and a secondpatch with one or more light-emitting components and correspondinglight-receiving components.

In another embodiment, illustrated in FIGS. 2 and 3, a device 200 isprovided comprising one or more light sources 220, each emittingselected wavelengths of light in the 400 nm to 1000 nm range. Each lightsource 220 is coupled with at least two photodetectors 230 each adaptedto receive light emitted at a given frequency. The device 200 is usefulto simultaneously measure multiple cardiac blood vessel pulses, such asjugular venous pulse as well as carotid arterial pulse. As one of skillin the art will appreciate, in the case of multiple light sources 220,each light source is turned on in sequence, and the amplitude of lightemitted from the light source(s) is modulated at a selected frequency,such as 10 kHz or 20 kHz. Alternatively, light emitted by a single lightsource 220 can be sequentially modulated at two alternating frequencies,such as 10 kHz and 20 kHz. The output from the photodetectors (e.g.current/voltage) is filtered at a frequency selected to correlate with agiven frequency emitted from a light source, for example, using a bandpass filter which allows a selected frequency, such as a 10 kHz or 20kHz signal, to pass through but blocks other frequency components in thesignal.

Each light source 120/220 may be any suitable light source such as alaser diode (e.g. RLT7605G, 760 nm, 5 mW, sm, 9.0 mmh, or RLT8510MG, 850nm, 10 mW, sm, 5.6 mm), a light emitting diode (LED) or a broadbandlight source emitting a selected wavelength in the range of 400 nm to1000 nm, for example, a wavelength in the range of 780 nm and 850 nm. Inan embodiment, a single light source is adapted to emit light in two ormore wavelengths, e.g. by association with a frequency oscillator. Thelight source 120/220 is powered by an appropriate power supply 118 suchas a 12V DC power supply. Light from the light source 120/220 isdirected to at least one external tissue site on the patient that iswithin close proximity to the internal jugular vein. Thus, the neck, forexample, represents a suitable site for placement of the patch probe.

Light from the light source 120/220 may be directed or focussed by anoptical lens into a transmitting means, such as transmitting opticalfibre bundles, for transmission to the selected patient site. Receivingmeans, such as optical fibre bundles, may also be used to receive lightthat is reflected/transmitted from the patient site and convey thislight to a photodetector 130/230. As one of skill in the art willappreciate, each fibre optic bundle will incorporate fibres manufacturedof material appropriate for the transmission of the wavelength of thelight emitted from the light source 120/220. For example, if the lightsource 120/220 emits in the visible wavelength range, both multiple modeplastic and glass optical fibres may be used. The number and diameter ofthe fibres in the fibre optic bundle is optimized empirically to providethe highest signal to noise ratio in a given application. Thetransmitting and receiving optical fibre bundles are set in the patchprobe, either at distinct spaced sites or they may be combined togetherat a single site. Optical mirrors may be utilized to direct or reflectlight from the transmitting fibre bundle into the tissue at the selectedpatient site, and to direct reflected or transmitted light from thepatient site into a receiving fibre bundle.

It will also be appreciated that a combination of the foregoingembodiments may be utilized in the device. For example, the light source120/220 may be set directly in the probe 128/228 to deliver light to thepatient site, while the reflected/transmitted light is received byoptical fibres for delivery to the photodetector 130/230. A converseembodiment may also be used in which the probe 128/228 comprisestransmitting optical fibres to deliver light from the light source tothe patient site, and a photodetector 130/230 set directly in the probeto receive the reflected/transmitted light. Accordingly, the lightsource 120/220 and photodetector 130/230 are each coupled to the probe(e.g. attached to, integrally formed with or set directly in the probe).

The distance between the component delivering light to the patient site(light source or transmitting optical fibres) and the componentreceiving light from the patient site (photodetector or receivingoptical fibres) may vary depending on the nature of each of thecomponents, while a typical distance is generally between 2 and 4 cm,for example, 3 cm.

The patch probe 128/228 may be made out of any material suitable tosupport the electronic/optical components it houses, e.g. light source,photodetector, optical fibres or mirrors, and which is compatible forplacement on the skin. An example of one such suitable material ismedical rubber. The patch may be held in position manually, may be heldin position by adhesives (one side of the patch may be coated with amaterial that is adhesive to skin such as a hydro gel adhesive) or maybe adapted to be held in place with straps that can be tied or otherwisesecured. Opposing ends of the band may also include an adhesive materialsuch as Velcro to facilitate their attachment and to hold the device inplace.

The photodetector 130/230 translates received reflected/transmittedlight into a recordable output such as current or voltage. An example ofa suitable photodetector for use in the present device is a siliconphoto diode (e.g. Hamamatsu S8553). Condensor lenses may beincorporated, if required, to refocus the reflected or transmitted beamof light to be received by the photodetector. As will be understood by aperson skilled in the art, silicon photodiodes are semiconductor lightsensors that generate a current or voltage when the P-N junction in thesemiconductor is illuminated by light. Accordingly, the photodetectorprovides a current/voltage signal in response to the received lightsignal. Thus, the current/voltage signal output generated by thephotodetector is proportional to the instantaneous light intensity ofthe light signal received at the photodetector. Accordingly, thephotodetector provides a time-varying output (e.g. current/voltage as afunction of time) which is dependent upon the received light and itscharacteristics.

In addition to providing a method for determining cerebral tissueoxygenation in a patient, in another aspect of the invention, a systemuseful to determine cerebral tissue oxygenation in a patient is providedas illustrated in FIGS. 4-6. The system comprises a first module 20, forexample comprising a device 100 or 200, useful to optically obtainjugular venous output signals against time from the patient at selectedwavelengths of light, a second module 22 e.g. a pulse oximeter, usefulto obtain cardiac arterial output signals at selected wavelengths oflight, e.g. based on carotid arterial pulse, from the patient, and asignal processing module 40 which receives output signals from the firstand second modules, separates the cardiac arterial output signalsobtained at the selected wavelengths of light, e.g. first and secondwavelengths of light, from the corresponding jugular venous outputsignals, e.g. first and second jugular venous output signals, to yieldcerebral pulse output signals, e.g. first and second cerebral pulseoutput signals, and calculates cerebral tissue oxygenation therefrom.The signal processing module 40 may also be operable to digitize theoutput of each device into a visual output for presentation on a displayunit, e.g. a monitor. Alternatively, the signal processing unit isadapted to calculate average cerebral tissue oxygenation based on thejugular venous output signals, cardiac arterial oxygenation based on thecardiac arterial output signals, and then provide an estimate ofcerebral oxygenation consumption based on the difference of internaljugular venous oxygenation and cardiac arterial oxygenation.

The signal processing module 40 may include one or more microprocessors(e.g. digital signal processor, Texas Instruments) or digitalacquisition boards to convert the analogue signal (e.g. current/voltage)received from the first and second modules to a digital signal andperform signal processing such as signal filtering using fouriertransform, and a display unit, such as a monitor, which is incommunication with or connected to the microprocessor(s) and functionsto display one or more signals as a waveform through a user interface.The display may include a trend curve plot and an oxygenation value.

Alternatively, as will be understood by a person of skill in the art,the signal processing module 40 may be separate from the display unit42, and in communication with an external display unit for presentingthe output of the signal processing module thereon. For convenience, themonitor may be portable, and battery operated. According to anotherembodiment, the signal processing module may further comprise analgorithm processing unit 41 adapted to calculate cerebral tissueoxygenation as outlined based on determined cerebral venous outputvalues.

Referring to FIG. 5, the signal processing module 40 can be implementedon one or more respective computing device(s) 101. The devices 101 ingeneral can include a network connection interface 200, such as anetwork interface card or a modem, coupled via connection 218 to adevice infrastructure 204. The connection interface 200 is connectableduring operation of the device(s) 101 to a network 11 (e.g. an intranetand/or an extranet such as the Internet) which enables the device(s) 101to communicate with each other as appropriate. The network 11 can, forexample, support the communication of the output signal (e.g.current/voltage signal) provided by the photodetector 130/230 to thesignal processing module 40.

The device(s) 101 may also have a user interface 202 coupled to thedevice infrastructure 204 by connection 222 to interact with a user. Theuser interface 202 can include one or more user input devices such as,but not limited to, a QWERTY keyboard, a keypad, a trackwheel, a stylus,a mouse, a microphone and a user output device such as an LCD screendisplay and/or a speaker. If the screen is touch sensitive, then thedisplay can also be used as the user input device as controlled by thedevice infrastructure 204.

Operation of the device(s) 101 is facilitated by the deviceinfrastructure 204. The device infrastructure 204 includes one or morecomputer processors 208 (e.g. a Digital Signal Processor) and caninclude an associated memory 210 (e.g. a random access memory). Thecomputer processor 208 facilitates performance of the computing device101 configured for the intended task through operation of the networkinterface 200, the user interface 202 and other applicationprograms/hardware 207 of the computing device 101 by executingtask-related instructions. These task-related instructions may beprovided by an operating system and/or software applications 207 locatedin the memory 210, and/or by operability that is configured into theelectronic/digital circuitry of the processor(s) 208 designed to performthe specific task(s). Further, it is recognized that the deviceinfrastructure 204 may include a computer readable storage medium 212coupled to the processor 208 for providing instructions to the processor208. The computer readable medium 212 can include hardware and/orsoftware such as, by way of example only, magnetic disks, magnetic tape,optically readable medium such as CD/DVD ROMS, and memory cards. In eachcase, the computer readable medium 212 may take the form of a smalldisk, floppy diskette, cassette, hard disk drive, solid-state memorycard or RAM provided in the memory module 210. It should be noted thatthe above listed examples of computer readable media 212 may be usedeither alone or in combination. The device memory 210 and/or computerreadable medium 212 may be used to store, for example, the desiredoutput (e.g. pressure waveform) for use in processing of the signalreceived from the photodetector 130/230.

Further, it is recognized that the computing device(s) 101 may includeexecutable applications 207 comprising code or machine readableinstructions for implementing predetermined functions/operationsincluding those of an operating system. The processor 208 as used hereinis a configured device and/or set of machine-readable instructions forperforming operations as described by example above. As used herein, theprocessor 208 may comprise any one or combination of, hardware,firmware, and/or software. The processor 208 acts upon information bymanipulating, analyzing, modifying, converting or transmittinginformation for use by an executable procedure or an information device,and/or by routing the information with respect to an output device. Theprocessor 208 may use or comprise the capabilities of a controller ormicroprocessor, for example. Accordingly, the functionality of thesignal processing module 40 and/or the photodetector 130/230 may beimplemented in hardware, software or a combination of both. Accordingly,the use of a processor 208 as a device and/or as a set ofmachine-readable instructions is hereafter referred to generically as aprocessor/module for the sake of simplicity.

It will be understood that the computing device(s) 101 may be, forexample, personal computers, personal digital assistants, mobile phones,and content players. Further, it is recognised that each servercomputing device 101, although depicted as a single computer system, maybe implemented as a network of computer processors, as desired.

Referring to FIG. 4, the signal processing module 40 may execute analgorithm (e.g. via the algorithm processing module 41) to translate thesignals received by the photodetectors/pulse oximeter to a waveform. Thewaveform is the time varying component of the optical signal which canbe translated into cerebral tissue oxygenation.

In use, a suitable patch probe of the first module of the system,comprising light source(s) and photodetectors, is generally placed onthe neck of a patient at a site near the internal jugular vein. It isdesirable for the patient to be lying down at about a 30 degree inclinefrom the horizontal. The patient maintains regular breathing during theprocess of measuring the pulse of the blood vessel. Light from the lightsource is either reflected off of, or transmitted through, the targetsite on the patient's neck, and detected by the photodetector. Thephotodetector translates the detected light into an output signal (e.g.current/voltage) that may be digitized for expression as amplitude as afunction of time to result in a jugular venous output signal (waveform).Simultaneously, a carotid artery output signal is obtained using thesecond module of the system, e.g. pulse oximeter. The output signals arereceived by the signal processing module to be processed, e.g.generation of cerebral pulse output signals, calculation of cerebraltissue oxygenation, digitization, and optionally display.

In another embodiment, a method and system for measuring local cerebraltissue oxygenation is provided. Such a method and system are useful tomonitor cerebral blood oxygenation for early detection of localizedcerebral tissue ischemic stroke.

The method comprises determining blood oxygenation measured from theexternal jugular vein (EJ), the internal jugular vein (IJ), cardiacartery (cardiac) and a cerebral site (measures oxygenation in scalp,skull and small portion of cerebral tissue). The external jugular veincontains, for the most part, venous blood from facial tissue (which ispart of the scalp) flowing back to the heart, and thus, may be used todetermine the venous oxygenation status of the scalp. The internaljugular vein contains venous blood from cerebral tissue/brain tissueflowing back to heart, and thus, may be used to determine the overalloxygenation status of cerebral tissues. The external and internaljugular veins are substantially parallel along the neck separatedsomewhat (e.g. by a few centimeters). The internal jugular vein istowards the front of neck and the external jugular vein is towards theears. There are standard practices to visualize the internal andexternal jugular veins in order to determine blood oxygenation of thesevessels. Blood oxygenation measured on a cerebral site, e.g. the head,provides the oxygenation of mixed vascular blood (vein and arterial)within the tissue underneath the site (e.g. mainly scalp, skull and asmall portion of actual cerebral tissue). Blood oxygenation of thecardiac artery provides the arterial blood oxygenation value of thescalp, since arterial blood oxygenation is the same over the entirebody.

Local cerebral tissue oxygenation (StO2) as obtained from a cerebralsite as above may be expressed as the weighted average of scalp venousoxygenation (SvO2_scalp), scalp arterial oxygenation (SaO2_scalp) andcerebral tissue venous oxygenation (SvO2_cerebral) since the majority ofblood vessels on the surface of brain are veins. This is summarized bythe following equation:StO2=A×SvO2_scalp+B×SvO2_cerebral+C×SaO2_scalp  (6)Parameters A, B, C are related to the spatial distribution and volume ofcorresponding blood vessels and the scattering and absorption propertiesof each of the tissues. Since scalp tissue is part of the facial tissue,SvO2_scalp, can be represented by SvO2_EJ (as above, the bloodoxygenation obtained from the external jugular is facial venousoxygenation). The average cerebral venous oxygenation, SvO2_cerebral,can be represented by SvO2_IJ (as above), and SaO2_scalp can berepresented by cardiac arterial oxygenation determined by pulse oximetrysince arterial oxygenation is generally the same over the entire body.Thus, in view of the foregoing, equation (6) may be rewritten as:StO2=A×SvO2_EJ+B×SvO2_IJ+C×SaO2  (7)

Thus, the present method of monitoring local cerebral blood oxygenationin a patient comprises the steps of: determining the venous bloodoxygenation from the scalp by generating at least first and secondoutput signals of change in blood volume as current or voltage over timeusing at least one photodetector based on the reflection or transmissionof at least first and second wavelengths of light from at least onelight source, wherein the light is applied to the neck of the patient inthe proximity of the external jugular vein; determining the averagecerebral venous oxygenation by generating at least first and secondoutput signals of change in blood volume as current or voltage over timeusing at least one photodetector based on the reflection or transmissionof at least first and second wavelengths of light from at least onelight source, wherein the light is applied to the neck of the patient inthe proximity of the internal jugular vein; determining local bloodoxygenation at one or more cerebral sites by generating at least firstand second output signals of change in blood volume as current orvoltage over time using at least one photodetector based on thereflection or transmission of at least first and second wavelengths oflight from at least one light source, wherein the light is applied tothe head of the patient in the proximity of the one or more cerebralsites; and determining cerebral arterial blood oxygenation by generatingat least first and second cardiac arterial output signals as current orvoltage of change in blood volume over time using a pulse oximeter forthe first and second wavelengths of light; and comparing the localcerebral blood oxygenation to the average cerebral blood oxygenation,scalp venous blood oxygenation and scalp arterial oxygenation using aprocessor to identify changes in one or more of these to detect cerebralischemia.

The conditions of this method of monitoring local cerebral bloodoxygenation are similar to those used in a method for determiningcerebral tissue oxygenation as described above. For example, the firstand second wavelengths of light are each in the range of 400 nm to 1000nm. Light transmission or reflection is detected in each case, and morethan two wavelengths of light may be utilized which may provide a moreaccurate result, e.g. reduce error.

Thus, the present method is useful to monitor for and identify a changein cerebral tissue oxygenation. For example, ischemic stroke (in whichthere is a blockage of a cerebral vessel), can be detected by monitoringtissue oxygenation, local cerebral oxygenation (StO2), SvO2_EJ, SvO2_IJ(which is the average cerebral oxygenation, of the whole brain) andSaO2. If a drop or decrease in local cerebral oxygenation (StO2) occurs,but no change in SvO2_EJ, SvO2_JJ and SaO2, then a blockage of a localcerebral vessel has occurred. If there is a change in average cerebraloxygenation (SvO2_IJ), but not in local cerebral oxygenation (StO2),then there has also been a drop in cerebral oxygenation but it is inanother part of the brain, and further probing at different cerebralsites can then be conducted to determine the location of the problem. Inthis regard, multiple cerebral sites may be simultaneously monitored inorder to more readily identify the cerebral location of a drop in bloodoxygenation, and thereby identify a cerebral site of ischemia. If thereis a simultaneous change in local cerebral oxygenation (StO2), as wellas in one of SvO2_EJ or SaO2, then the change in oxygenation hasoccurred in scalp venous or scalp arterial oxygenation, and is not as aresult of a drop in cerebral oxygenation. Thus, simultaneouslymonitoring all four oxygenation measurements leads to a much morereliable determination of local cerebral tissue oxygenation.

A system useful to monitor local cerebral tissue oxygenation in apatient is provided as illustrated in FIG. 9. The system 300 comprises afirst module 320 to optically obtain internal jugular venous outputsignals against time from the patient at selected wavelengths of lightto determine average cerebral blood oxygenation (SvO2_cerebral), asecond module 322 e.g. a pulse oximeter, to obtain cardiac arterialoutput signals at selected wavelengths of light, e.g. based on carotidarterial pulse, from the patient to determine scalp arterial bloodoxygenation (SaO2 scalp), a third module 324 to optically obtainexternal jugular venous output signals against time at selectedwavelengths of light to determine venous scalp blood oxygenation(SvO2_scalp), a fourth cerebral module 326 to optically obtain outputsignals against time at a cerebral site (StO2), and a signal processingmodule 340 which receives output signals from the four modules, andcalculates StO2, SvO2_scalp, SvO2_cerebral and SaO2_scalp for use in amethod of monitoring local cerebral blood oxygenation as described.

Modules 320, 324 and 326 comprise at least one light source to emitlight at one or more selected wavelengths of light, and at least onephotodetector to receive transmitted or reflected light at eachwavelenth and translate the received light into the output signal(change in blood volume), as current or voltage, over time. Thearrangement of light source(s) and photodetector(s) in each module maybe the same or different as shown in FIGS. 1-3.

In order to monitor cerebral blood oxygenation at more than one cerebralsite, or at multiple cerebral sites, the system may comprise multiplecerebral modules 326 for placement at various sites on a patient head.In this way, a particular cerebral location of ischemia may beidentified more readily. In particular, a drop or decrease in cerebraloxygenation (StO2) at one of the cerebral modules is indicative of ablockage of a local cerebral vessel at or near the cerebral site beingmonitored, and this would allow further analysis and any requiredimmediate action to be taken in a specific manner. As one of skill inthe art will appreciate, the signal processing module 340 may be adaptedto receive output signals from one, two or multiple cerebral modules,and to calculate the blood oxygenation at each of these modules.

As described, the signal processing module 340 may include one or moremicroprocessors or digital acquisition boards to convert the analoguesignal (e.g. current/voltage) received from each of the modules to adigital signal and perform signal processing such as signal filteringusing fourier transform, and a display unit, such as a monitor, which isin communication with or connected to the microprocessor(s) andfunctions to display one or more signals in any desired format, e.g.waveform(s), oxygenation values, or any other format.

Embodiments of the present invention are described by reference to thefollowing specific example which is not to be construed as limiting.

EXAMPLE 1 Measurement of Cerebral Oxygenation in a Patient

The cerebral tissue oxygenation of a human subject was obtained using asystem as shown in FIG. 6. The patient lay on a chair at about a 30degree recline. The first module of the system, e.g. sensor patch, wasplaced on the neck of the patient at a site over the internal jugularvein. The second module (oximeter sensor patch) was placed on the indexfinger tip of the patient. While the patient maintained normalbreathing, jugular venous pulse (output signal) was obtained from thefirst module and cardiac arterial pulse (output signal) was obtainedfrom the second module. The signals were received by the signalprocessing module, processed as described above, to yield a jugularvenous waveform (FIG. 7A), a cardiac arterial waveform (FIG. 7B) and acerebral venous waveform (FIG. 7C). The amplitude of the detectedsignals is represented along the y-axis while the x-axis representstime. The signal processing module utilized this signal information tocalculate cerebral oxygenation which can be displayed on auser-interface as a waveform and an oxygenation value as shown in FIG.8.

I claim:
 1. A system comprising: 1) a first module for opticallygenerating at least first and second internal jugular venous outputsignals as current or voltage based on change in blood volume over timeat at least first and second wavelengths of light, wherein said firstmodule comprises at least one light source to emit the light and atleast one photodetector to receive transmitted or reflected light ofeach wavelength from the light source and translate it into the outputsignals; 2) a second module comprising a pulse oximeter for generatingat least first and second cardiac arterial output signals over time atthe first and second wavelengths of light, respectively; and 3) a signalprocessing means that functions to calculate average cerebral bloodoxygenation based on the output signals from the first module, arterialblood oxygenation based on the output signals from the second module andcerebral tissue oxygenation based on the difference between averagecerebral blood oxygenation and arterial blood oxygenation.
 2. The systemof claim 1, further comprising: a third module for optically generatingat least first and second external jugular venous output signals ascurrent or voltage based on change in blood volume over time at at leastfirst and second wavelengths of light, wherein said third modulecomprises at least one light source to emit the light and at least onephotodetector to receive transmitted or reflected light from the lightsource and translate it into the output signals; and at least onecerebral module for optically generating at least first and secondcerebral site output signals as current or voltage based on change inblood volume over time at at least first and second wavelengths oflight, wherein said cerebral module comprises at least one light sourceto emit the light and at least one photodetector to receive transmittedor reflected light from the light source and translate it into theoutput signals, wherein the signal processing means additionallyfunctions to calculate scalp venous blood oxygenation based on theoutput signals from the third module and local cerebral bloodoxygenation based on the output signals from the cerebral module.
 3. Thesystem of claim 2, comprising multiple cerebral modules, wherein saidsignal processing means functions to calculate local cerebral bloodoxygenation for each of said modules based on output signals generatedby said modules.
 4. A system as defined in claim 2, wherein the firstand second wavelengths of light are within the range of about 400-1000nm.
 5. A system as defined in claim 4, wherein the first wavelength isabout 690 nm and the second wavelength is about 830 nm.
 6. The system ofclaim 1, wherein the signal processing means is adapted to subtractarterial blood oxygenation from average cerebral blood oxygenation toyield a corrected cerebral tissue oxygenation value.
 7. A system asdefined in claim 1, wherein the first and second wavelengths of lightare within the range of about 400-1000 nm.
 8. A system as defined inclaim 7, wherein the first wavelength is about 690 nm and the secondwavelength is about 830 nm.
 9. A system as defined in claim 7, whereinthe signal processing means comprises one or more microprocessors and adisplay unit.
 10. A system as defined in claim 1, wherein said firstmodule comprises a light source to emit each wavelength of light and aphotodetector for each light source.
 11. The application has beenamended as follows: 1) determining the average cerebral venous bloodoxygenation in a patient using a processor based on at least first andsecond output signals of change in blood volume as current or voltagegenerated by at least one photodetector wherein said output signals arebased on the reflection or transmission of at least first and secondwavelengths of light from at least one light source, wherein the lightis applied to the neck of the patient in the proximity of the internaljugular vein; 2) determining cerebral arterial blood oxygenation in thepatient using a processor based on at least first and second cardiacarterial output signals over time generated using a pulse oximeter forthe first and second wavelengths of light; and 3) calculating cerebraltissue oxygenation based on the difference between average cerebralvenous blood oxygenation and cerebral arterial blood oxygenation. 12.The method of claim 11, additionally comprising the steps of:determining scalp venous blood oxygenation in the patient using aprocessor by generating at least first and second output signals ofchange in blood volume as current or voltage over time using at leastone photodetector, wherein the output signals are based on thereflection or transmission of at least first and second wavelengths oflight from at least one light source, wherein the light is applied tothe neck of the patient in the proximity of the external jugular vein;determining local cerebral blood oxygenation at one or more cerebralsites in the patient using a processor by generating at least first andsecond output signals of change in blood volume as current or voltageover time using at least one photodetector, wherein the output signalsare based on the reflection or transmission of at least first and secondwavelengths of light from at least one light source, wherein the lightis applied to the head of the patient in the proximity of the one ormore cerebral sites; and further comparing local cerebral bloodoxygenation to the average cerebral venous blood oxygenation, scalpvenous blood oxygenation and scalp arterial oxygenation using aprocessor to identify changes in one or more of these to identifycerebral ischemia.